Physiological ER Stress Mediates the Differentiation of Fibroblasts.
Physiological ER Stress Mediates the Differentiation of Fibroblasts.
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DOI：
10.1371/journal.pone.0123578
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Katayama T
中科院分区：
文献类型：
--
作者：
Matsuzaki S;Hiratsuka T;Taniguchi M;Shingaki K;Kubo T;Kiya K;Fujiwara T;Kanazawa S;Kanematsu R;Maeda T;Takamura H;Yamada K;Miyoshi K;Hosokawa K;Tohyama M;Katayama T
近年来，越来越多的研究表明内质网（ER）应激信号在成肌细胞和成骨细胞等多种组织和细胞分化中的重要性。分泌细胞在其分泌蛋白成熟过程中容易受到ER应激。皮肤成纤维细胞产生并释放几种蛋白质，例如胶原、基质金属蛋白酶（MMP）、金属蛋白酶的组织抑制剂（TIMP）和糖胺聚糖（GAG），并且这些蛋白质的产生在伤口部位增加。成纤维细胞向肌成纤维细胞的分化是伤口愈合的关键因素之一，TGF-β可以诱导成纤维细胞向肌成纤维细胞分化，肌成纤维细胞表达α-平滑肌肌动蛋白。分化良好的肌成纤维细胞显示胶原蛋白和TGF-β的产生增加，并导致伤口愈合。在这项研究中，我们研究了ER应激信号对成纤维细胞分化的影响，这是伤口愈合所需的，使用组成性ER应激激活的原代培养的成纤维细胞。与对照成纤维细胞相比，在没有TGF-β刺激的情况下，细胞表达阳性α-平滑肌肌动蛋白信号。凝胶收缩试验表明，ER应力处理的原代成纤维细胞引起更强的收缩胶原凝胶比对照细胞。这些结果表明，ER应激信号可以加速损伤部位成纤维细胞向肌成纤维细胞的分化。目前的研究结果可能为开发治疗方法以改善伤口愈合提供重要见解。
Recently, accumulating reports have suggested the importance of endoplasmic reticulum (ER) stress signaling in the differentiation of several tissues and cells, including myoblasts and osteoblasts. Secretory cells are easily subjected to ER stress during maturation of their secreted proteins. Skin fibroblasts produce and release several proteins, such as collagens, matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs) and glycosaminoglycans (GAGs), and the production of these proteins is increased at wound sites. Differentiation of fibroblasts into myofibroblasts is one of the key factors for wound healing and that TGF-β can induce fibroblast differentiation into myofibroblasts, which express α-smooth muscle actin. Well-differentiated myofibroblasts show increased production of collagen and TGF-β, and bring about wound healing. In this study, we examined the effects of ER stress signaling on the differentiation of fibroblasts, which is required for wound healing, using constitutively ER stress-activated primary cultured fibroblasts. The cells expressed positive α-smooth muscle actin signals without TGF-β stimulation compared with control fibroblasts. Gel-contraction assays suggested that ER stress-treated primary fibroblasts caused stronger shrinkage of collagen gels than control cells. These results suggest that ER stress signaling could accelerate the differentiation of fibroblasts to myofibroblasts at injured sites. The present findings may provide important insights for developing therapies to improve wound healing.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
通讯作者：
Tohyama, Masaya
影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
21.3
作者：
Murakami, Tomohiko;Saito, Atsushi;Imaizumi, Kazunori
通讯作者：
Imaizumi, Kazunori
影响因子：
10
作者：
GLUCKSMANN, A
通讯作者：
GLUCKSMANN, A
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D